Fig. 9
From: Disseminated intravascular coagulation phenotype is regulated by the TRPM7 channel during sepsis
TRPM7 suppression protects from endotoxemia-induced procoagulant phenotype, increased death and risk of death during endotoxemia. A Experimental strategy for in vivo endotoxemia and AdV infection in rats. Rats were divided in 4 groups. Group 1: AdVCTRL-injected + saline-treated. Group 2: AdVCTRL-injected + endotoxin-treated. Group 3: AdVshTRPM7-injected + saline-treated. Group 4: AdVshTRPM7-injected + endotoxin-treated. Endotoxin was administrated at 10 mg/kg. AdVs were injected every 24 h from 48 before to 72 h after induction (6 injections). After treatment, blood samples were collected to determine collagen-induced platelet aggregation (B), ADP-induced platelet aggregation (C), platelet count (D), plasma D-dimer levels (E), bleeding time (F), and clotting time (G). AdVCTRL-injected + saline-treated (grey circles), AdVCTRL-injected + endotoxin-treated (red circles), AdVshTRPM7-injected + saline-treated (green circles), AdVshTRPM7-injected + endotoxin-treated (blue circles) rats. Statistical differences were assessed by one-way analysis of variance (ANOVA) followed by Dunn's post hoc test. *: p < 0.05, **: p < 0.01, ***: p < 0.001, ****: p < 0.0001, compared with the saline-treated condition. H TRPM7 mRNA and protein expression in RMEC from AdVCTRL-injected + saline-treated (Saline, grey circles) and AdVCTRL-injected + endotoxin-treated rats (Endo, red circles). Statistical differences were assessed by student’s t-test (Mann–Whitney) (N = 16). **p < 0.01, ***p < 0.001, compared with the survivor patients’ group. Results showed as mean ± SEM. I Survival (Kaplan–Meier) curves comparing AdVCTRL-injected + saline-treated (grey line) (N = 16), AdVCTRL-injected + endotoxin-treated (red line) (N = 16), AdVshTRPM7-injected + saline-treated (green line) (N = 16), AdVshTRPM7-injected + endotoxin-treated (blue line) (N = 16) rats. * and #, p = 0.002 (log-rank (Mantel–Cox) test) when comparing AdVCTRL-injected + endotoxin-treated versus AdVshTRPM7-injected + saline-treated condition (*) and AdVshTRPM7-injected + endotoxin-treated (#) rats. ¶ and §, p = 0.0008 (Gehan-Breslow-Wilcoxon test) when comparing AdVCTRL-injected + endotoxin-treated versus AdVshTRPM7-injected + saline-treated condition (¶) and AdVshTRPM7-injected + endotoxin-treated (§) rats. J Contingency analyses performed to determine relative risk between AdVCTRL-injected + endotoxin-treated (N = 16), AdVshTRPM7-injected + saline-treated (N = 16) and AdVshTRPM7-injected + endotoxin-treated (N = 16) rats showed in I. ‡, p < 0.05, compared with the AdVshTRPM7-injected + saline-treated condition. K TRPM7 mRNA and protein expression in RMEC from surviving (grey circles) and non-surviving (red circles) AdVCTRL-injected + endotoxin-treated rats. Statistical differences were assessed by student’s t-test (Mann–Whitney) (N = 16) **p < 0.01, compared with the survivor patients’ group. Results showed as mean ± SEM. L Correlation analyses between TRPM7 mRNA and protein expression with survival time in RMEC from non-surviving rats. The relationships between variables were assessed by means of correlation analysis using Spearman’s correlation coefficients and linear regression